| H00770 | |
| H number | H00770 |
| Name | Congenital myasthenic syndrome |
| Description | Congenital myasthenic syndromes (CMS) are a heterogenous group of genetic disorders caused by mutations in several proteins that compose the neuromuscular junction (NMJ) apparatus on which synaptic formation and function depend. The majority are recessively inherited. The disorders of the NMJ cause weakness and fatigue. |
| Category | Nervous system disease |
| Network | - |
| Gene | (CMS1A/1B) CHRNA1 [HSA:1134] [KO:K04803] (CMS2A/2C) CHRNB1 [HSA:1140] [KO:K04812] (CMS3A/3B/3C) CHRND [HSA:1144] [KO:K04816] (CMS4A/4B/4C) CHRNE [HSA:1145] [KO:K04817] (CMS5) COLQ [HSA:8292] [KO:K26586] (CMS6) CHAT [HSA:1103] [KO:K00623] (CMS7A/7B) SYT2 [HSA:127833] [KO:K19902] (CMS8) AGRN [HSA:375790] [KO:K06254] (CMS9) MUSK [HSA:4593] [KO:K05129] (CMS10) DOK7 [HSA:285489] [KO:K24038] (CMS11) RAPSN [HSA:5913] [KO:K24924] (CMS12) GFPT1 [HSA:2673] [KO:K00820] (CMS13) DPAGT1 [HSA:1798] [KO:K01001] (CMS14) ALG2 [HSA:85365] [KO:K03843] (CMS15) ALG14 [HSA:199857] [KO:K07441] (CMS16) SCN4A [HSA:6329] [KO:K04837] (CMS17) LRP4 [HSA:4038] [KO:K20051] (CMS18) SNAP25 [HSA:6616] [KO:K18211] (CMS19) COL13A1 [HSA:1305] [KO:K16617] (CMS20) SLC5A7 [HSA:60482] [KO:K14387] (CMS21) SLC18A3 [HSA:6572] [KO:K14636] (CMS22) PREPL [HSA:9581] [KO:K22582] (CMS23) SLC25A1 [HSA:6576] [KO:K15100] (CMS24) MYO9A [HSA:4649] [KO:K10360] (CMS25) VAMP1 [HSA:6843] [KO:K08510] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 8C61 ICD-10: G70.2 MeSH: D020294 OMIM: 601462 608930 616313 616314 616321 616322 616323 605809 616324 608931 603034 254210 616040 619461 615120 616325 254300 616326 610542 614750 616228 616227 614198 616304 616330 616720 617143 617239 616224 618197 618198 618323 |
| Reference | PMID:19593127 AUTHORS Argov Z TITLE Management of myasthenic conditions: nonimmune issues. JOURNAL Curr Opin Neurol 22:493-7 (2009) DOI:10.1097/WCO.0b013e32832f15fa PMID:20547629 AUTHORS Spillane J, Beeson DJ, Kullmann DM TITLE Myasthenia and related disorders of the neuromuscular junction. JOURNAL J Neurol Neurosurg Psychiatry 81:850-7 (2010) DOI:10.1136/jnnp.2008.169367 PMID:8872460 (CMS1A CMS2A CMS4A) AUTHORS Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, Pruitt JN 2nd, Hutchinson DO, Brengman JM, Bren N, Sieb JP, Sine SM TITLE New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. JOURNAL Hum Mol Genet 5:1217-27 (1996) DOI:10.1093/hmg/5.9.1217 PMID:10195214 (CMS1B) AUTHORS Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM TITLE Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating. JOURNAL Nat Neurosci 2:226-33 (1999) DOI:10.1038/6326 PMID:10562302 (CMS2C) AUTHORS Quiram PA, Ohno K, Milone M, Patterson MC, Pruitt NJ, Brengman JM, Sine SM, Engel AG TITLE Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly. JOURNAL J Clin Invest 104:1403-10 (1999) DOI:10.1172/JCI8179 PMID:11782989 (CMS3A) AUTHORS Gomez CM, Maselli RA, Vohra BP, Navedo M, Stiles JR, Charnet P, Schott K, Rojas L, Keesey J, Verity A, Wollmann RW, Lasalde-Dominicci J TITLE Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms. JOURNAL Ann Neurol 51:102-12 (2002) DOI:10.1002/ana.10077 PMID:11435464 (CMS3B) AUTHORS Brownlow S, Webster R, Croxen R, Brydson M, Neville B, Lin JP, Vincent A, Newsom-Davis J, Beeson D TITLE Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. JOURNAL J Clin Invest 108:125-30 (2001) DOI:10.1172/JCI12935 PMID:16916845 (CMS3C) AUTHORS Muller JS, Baumeister SK, Schara U, Cossins J, Krause S, von der Hagen M, Huebner A, Webster R, Beeson D, Lochmuller H, Abicht A TITLE CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn. JOURNAL Brain 129:2784-93 (2006) DOI:10.1093/brain/awl188 PMID:8755487 (CMS4B) AUTHORS Ohno K, Wang HL, Milone M, Bren N, Brengman JM, Nakano S, Quiram P, Pruitt JN, Sine SM, Engel AG TITLE Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. JOURNAL Neuron 17:157-70 (1996) DOI:10.1016/s0896-6273(00)80289-5 PMID:8957026 (CMS4C) AUTHORS Engel AG, Ohno K, Bouzat C, Sine SM, Griggs RC TITLE End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit. JOURNAL Ann Neurol 40:810-7 (1996) DOI:10.1002/ana.410400521 PMID:9689136 (CMS5) AUTHORS Ohno K, Brengman J, Tsujino A, Engel AG TITLE Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. JOURNAL Proc Natl Acad Sci U S A 95:9654-9 (1998) DOI:10.1073/pnas.95.16.9654 PMID:11172068 (CMS6) AUTHORS Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham FJ, Engel AG TITLE Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. JOURNAL Proc Natl Acad Sci U S A 98:2017-22 (2001) DOI:10.1073/pnas.98.4.2017 PMID:25192047 (CMS7A) AUTHORS Herrmann DN, Horvath R, Sowden JE, Gonzalez M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmuller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S TITLE Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. JOURNAL Am J Hum Genet 95:332-9 (2014) DOI:10.1016/j.ajhg.2014.08.007 PMID:32250532 (CMS7B) AUTHORS Maselli RA, van der Linden H Jr, Ferns M TITLE Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C-terminal amino acid sequence. JOURNAL Am J Med Genet A 182:1744-1749 (2020) DOI:10.1002/ajmg.a.61579 PMID:19631309 (CMS8) AUTHORS Huze C, Bauche S, Richard P, Chevessier F, Goillot E, Gaudon K, Ben Ammar A, Chaboud A, Grosjean I, Lecuyer HA, Bernard V, Rouche A, Alexandri N, Kuntzer T, Fardeau M, Fournier E, Brancaccio A, Ruegg MA, Koenig J, Eymard B, Schaeffer L, Hantai D TITLE Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. JOURNAL Am J Hum Genet 85:155-67 (2009) DOI:10.1016/j.ajhg.2009.06.015 PMID:15496425 (CMS9) AUTHORS Chevessier F, Faraut B, Ravel-Chapuis A, Richard P, Gaudon K, Bauche S, Prioleau C, Herbst R, Goillot E, Ioos C, Azulay JP, Attarian S, Leroy JP, Fournier E, Legay C, Schaeffer L, Koenig J, Fardeau M, Eymard B, Pouget J, Hantai D TITLE MUSK, a new target for mutations causing congenital myasthenic syndrome. JOURNAL Hum Mol Genet 13:3229-40 (2004) DOI:10.1093/hmg/ddh333 PMID:16917026 (CMS10) AUTHORS Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S, Newsom-Davis J, Burke G, Fawcett P, Motomura M, Muller JS, Lochmuller H, Slater C, Vincent A, Yamanashi Y TITLE Dok-7 mutations underlie a neuromuscular junction synaptopathy. JOURNAL Science 313:1975-8 (2006) DOI:10.1126/science.1130837 PMID:11791205 (CMS11) AUTHORS Ohno K, Engel AG, Shen XM, Selcen D, Brengman J, Harper CM, Tsujino A, Milone M TITLE Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. JOURNAL Am J Hum Genet 70:875-85 (2002) DOI:10.1086/339465 PMID:21310273 (CMS12) AUTHORS Senderek J, Muller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hubner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmuller H TITLE Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. JOURNAL Am J Hum Genet 88:162-72 (2011) DOI:10.1016/j.ajhg.2011.01.008 PMID:22742743 (CMS13) AUTHORS Belaya K, Finlayson S, Slater CR, Cossins J, Liu WW, Maxwell S, McGowan SJ, Maslau S, Twigg SR, Walls TJ, Pascual Pascual SI, Palace J, Beeson D TITLE Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. JOURNAL Am J Hum Genet 91:193-201 (2012) DOI:10.1016/j.ajhg.2012.05.022 PMID:23404334 (CMS14 CMS15) AUTHORS Cossins J, Belaya K, Hicks D, Salih MA, Finlayson S, Carboni N, Liu WW, Maxwell S, Zoltowska K, Farsani GT, Laval S, Seidhamed MZ, Donnelly P, Bentley D, McGowan SJ, Muller J, Palace J, Lochmuller H, Beeson D TITLE Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. JOURNAL Brain 136:944-56 (2013) DOI:10.1093/brain/awt010 PMID:12766226 (CMS16) AUTHORS Tsujino A, Maertens C, Ohno K, Shen XM, Fukuda T, Harper CM, Cannon SC, Engel AG TITLE Myasthenic syndrome caused by mutation of the SCN4A sodium channel. JOURNAL Proc Natl Acad Sci U S A 100:7377-82 (2003) DOI:10.1073/pnas.1230273100 PMID:24234652 (CMS17) AUTHORS Ohkawara B, Cabrera-Serrano M, Nakata T, Milone M, Asai N, Ito K, Ito M, Masuda A, Ito Y, Engel AG, Ohno K TITLE LRP4 third beta-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. JOURNAL Hum Mol Genet 23:1856-68 (2014) DOI:10.1093/hmg/ddt578 PMID:25381298 (CMS18) AUTHORS Shen XM, Selcen D, Brengman J, Engel AG TITLE Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. JOURNAL Neurology 83:2247-55 (2014) DOI:10.1212/WNL.0000000000001079 PMID:26626625 (CMS19) AUTHORS Logan CV, Cossins J, Rodriguez Cruz PM, Parry DA, Maxwell S, Martinez-Martinez P, Riepsaame J, Abdelhamed ZA, Lake AV, Moran M, Robb S, Chow G, Sewry C, Hopkins PM, Sheridan E, Jayawant S, Palace J, Johnson CA, Beeson D TITLE Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII alpha1 Chain. JOURNAL Am J Hum Genet 97:878-85 (2015) DOI:10.1016/j.ajhg.2015.10.017 PMID:27569547 (CMS20) AUTHORS Bauche S, O'Regan S, Azuma Y, Laffargue F, McMacken G, Sternberg D, Brochier G, Buon C, Bouzidi N, Topf A, Lacene E, Remerand G, Beaufrere AM, Pebrel-Richard C, Thevenon J, El Chehadeh-Djebbar S, Faivre L, Duffourd Y, Ricci F, Mongini T, Fiorillo C, Astrea G, Burloiu CM, Butoianu N, Sandu C, Servais L, Bonne G, Nelson I, Desguerre I, Nougues MC, Boeuf B, Romero N, Laporte J, Boland A, Lechner D, Deleuze JF, Fontaine B, Strochlic L, Lochmuller H, Eymard B, Mayer M, Nicole S TITLE Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea. JOURNAL Am J Hum Genet 99:753-761 (2016) DOI:10.1016/j.ajhg.2016.06.033 PMID:27590285 (CMS21) AUTHORS O'Grady GL, Verschuuren C, Yuen M, Webster R, Menezes M, Fock JM, Pride N, Best HA, Benavides Damm T, Turner C, Lek M, Engel AG, North KN, Clarke NF, MacArthur DG, Kamsteeg EJ, Cooper ST TITLE Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome. JOURNAL Neurology 87:1442-1448 (2016) DOI:10.1212/WNL.0000000000003179 PMID:24610330 (CMS22) AUTHORS Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG TITLE PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. JOURNAL Neurology 82:1254-60 (2014) DOI:10.1212/WNL.0000000000000295 PMID:26870663 (CMS23) AUTHORS Chaouch A, Porcelli V, Cox D, Edvardson S, Scarcia P, De Grassi A, Pierri CL, Cossins J, Laval SH, Griffin H, Muller JS, Evangelista T, Topf A, Abicht A, Huebner A, von der Hagen M, Bushby K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L, Lochmuller H TITLE Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. JOURNAL J Neuromuscul Dis 1:75-90 (2014) DOI:10.3233/JND-140021 PMID:27259756 (CMS24) AUTHORS O'Connor E, Topf A, Muller JS, Cox D, Evangelista T, Colomer J, Abicht A, Senderek J, Hasselmann O, Yaramis A, Laval SH, Lochmuller H TITLE Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome. JOURNAL Brain 139:2143-53 (2016) DOI:10.1093/brain/aww130 PMID:28253535 (CMS25) AUTHORS Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS, Pitt M, Bello OD, Rothman JE, Basel-Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H TITLE Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome. JOURNAL Ann Neurol 81:597-603 (2017) DOI:10.1002/ana.24905 |